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Hopkins Et Al. 2020 Cortisol and Giant Salamanders

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Hopkins Et Al. 2020 Cortisol and Giant Salamanders General and Comparative Endocrinology 285 (2020) 113267 Contents lists available at ScienceDirect General and Comparative Endocrinology journal homepage: www.elsevier.com/locate/ygcen Cortisol is the predominant glucocorticoid in the giant paedomorphic T hellbender salamander (Cryptobranchus alleganiensis) ⁎ William A. Hopkinsa, , Sarah E. DuRantb, Michelle L. Becka,c, W. Keith Rayd, Richard F. Helmd, L. Michael Romeroe a Dept of Fish and Wildlife Conservation, Virginia Tech, Blacksburg, VA 24061, USA b Dept of Biological Sciences, University of Arkansas, Fayetteville, AR 72701, USA c Dept. of Biology, Rivier University, Nashua, NH 03060, USA d Dept of Biochemistry, Virginia Tech, Blacksburg, VA 24061, USA e Dept of Biology, Tufts University, Medford, MA 02144, USA ARTICLE INFO ABSTRACT Keywords: Corticosterone is widely regarded to be the predominant glucocorticoid produced in amphibians. However, we Amphibian recently described unusually low baseline and stress-induced corticosterone profiles in eastern hellbenders Corticosterone (Cryptobranchus alleganiensis alleganiensis), a giant, fully aquatic salamander. Here, we hypothesized that hell- ACTH benders might also produce cortisol, the predominant glucocorticoid used by fishes and non-rodent mammals. Glucocorticoid To test our hypothesis, we collected plasma samples in two field experiments and analyzed them using multiple Paedomorphosis analytical techniques to determine how plasma concentrations of cortisol and corticosterone co-varied after 1) physical restraint and 2) injection with adrenocorticotropic hormone (ACTH), the pituitary hormone responsible for triggering the release of glucocorticoids from amphibian interrenal glands. Using liquid chromatography- mass spectrometry, we found that baseline and restraint-induced plasma concentrations of cortisol were more than five times those of corticosterone. We then demonstrated that plasma concentrations of both glucocorti- coids increased in response to ACTH in a dose-dependent manner, but cortisol concentrations were consistently higher (up to 10-fold) than corticosterone. Cortisol and corticosterone concentrations were not correlated with one another at basal or induced conditions. The extremely low plasma concentrations of corticosterone in hellbenders suggests that corticosterone could simply be a byproduct of cortisol production, and raises questions as to whether corticosterone has any distinct physiological function in hellbenders. Our results indicate that hellbenders produce cortisol as their predominant glucocorticoid, supporting a small and inconclusive body of literature indicating that some other amphibians may produce appreciable quantities of cortisol. We hypothesize that the use of cortisol by hellbenders could be an adaptation to their fully aquatic life history due to cortisol’s ability to fulfill both mineralocorticoid and glucocorticoid functions, similar to its functions in fishes. Giventhe large number of amphibian species that are fully aquatic or have aquatic life stages, we suggest that the broadly held assumption that corticosterone is the predominant glucocorticoid in all amphibians requires further scru- tiny. Ultimately, multi-species tests of this assumption will reveal the ecological factors that influenced the evolution of endocrine adaptations among amphibian lineages, and may provide insight into convergent evo- lution of endocrine traits in paedomorphic species. 1. Introduction demanding and “stressful” conditions (Greenburg and Wingfield, 1987; Herman, 1992; Norris and Carr, 2013; Wingfield and Romero, 2001; Corticosterone is widely regarded as the predominant glucocorti- Moore and Jessop, 2003). Anurans (frogs and toads) release corticos- coid produced in most amphibians in response to energetically terone when faced with a vast array of environmental stimuli including Abbreviations: ACTH, adrenocorticotropic hormone; EIA, enzyme immunoassay; HPLC, high-performance liquid chromatography; LC–MS, liquid chromatography mass spectrometry; MDLC, multi-dimensional liquid chromatography; RIA, radioimmunoassay; P4, Progesterone; 17OHP4, 17α-hydroxyprogesterone; DOC, 11- deoxycorticosterone; S, 11-deoxycortisol ⁎ Corresponding author. E-mail address: [email protected] (W.A. Hopkins). https://doi.org/10.1016/j.ygcen.2019.113267 Received 25 June 2019; Received in revised form 19 August 2019; Accepted 1 September 2019 Available online 03 September 2019 0016-6480/ © 2019 Elsevier Inc. All rights reserved. W.A. Hopkins, et al. General and Comparative Endocrinology 285 (2020) 113267 exposure to pollutants (Hopkins et al., 1997), capture and handling 2. Methods (Belden et al., 2010), pathogens (Gabor et al., 2013), pond drying (Denver, 1998), predators (Maher et al., 2013), competition 2.1. Study species (Glennemeier and Denver, 2002a), and food deprivation (Glennemeier and Denver, 2002a; Reeve et al., 2013). In addition, corticosterone Hellbenders are giant salamanders in the Family Cryptobranchidae, modulates energetically expensive anuran calling behaviors during the which only contains two other species globally (Andrias davidianus and reproductive season (Hopkins et al., 1997; Emerson and Hess, 2001; A. japonicus in China and Japan). All three species are considered im- Leary et al., 2006; Moore and Jessop, 2003; Eikenaar et al., 2012) and periled and population trends suggest they could eventually face ex- key developmental events associated with anuran metamorphosis tinction. In North America, there are two recognized subspecies of (Hayes, 1997; Denver, 1998; Wright et al., 2003). Likewise, Urodeles hellbenders; the eastern subspecies (Cryptobranchus alleganiensis alle- (salamanders) release corticosterone in response to an equally diverse ganiensis) and the Ozark subspecies (C. a. bishopi). Both subspecies have array of stimuli (e.g., Gendron et al., 1997; Homan et al., 2003; experienced precipitous population declines in the last few decades Cooperman et al., 2004; Schubert et al., 2009; Hopkins and DuRant, (Wheeler et al., 2003; Briggler et al., 2007; Foster et al., 2009), re- 2011; Ricciardella et al., 2010; Davis and Gabor, 2015; DuRant et al., sulting in the Ozark subspecies receiving federal protection and one 2015; but see Fonner and Woodley, 2015). Although generalizable evolutionarily distinct lineage of the eastern subspecies being con- patterns (e.g., corticosterone as the dominant glucocorticoid in am- sidered for similar status (USFWS 2011a,b, 2019). The last population phibians) are widespread in endocrinology, exceptions to these gen- stronghold for eastern hellbenders is believed to occur across portions eralizations can reveal important areas of ecological and evolutionary of Appalachia. In the area of Virginia where our work was conducted, divergence among taxa. the major threats to hellbender populations are most likely habitat We recently described unusual corticosterone profiles in eastern degradation, disease and parasitism, and direct human persecution hellbenders (Cryptobranchus alleganiensis alleganiensis), the only North (Hopkins and DuRant, 2011; Davis and Hopkins, 2013; DuRant et al., American member of the ancient giant salamander Family 2015; Hopkins et al., 2014; Hopkins et al., 2016; Jachowski and Cryptobranchidae. Hellbenders are obligate paedomorphs that display a Hopkins, 2018). number of unusual physiological, genetic, and morphological traits Hellbenders are large (up to 70 cm total length), long-lived compared to other amphibians (Nickerson and Mays, 1973; Jerrett and (> 30 years) fully aquatic salamanders that thrive in cool, well oxy- Mays, 1973; Sun and Mueller, 2014), but their endocrine physiology genated lotic habitats (Nickerson and Mays, 1973; Taber et al., 1975; remains poorly studied. We demonstrated that this giant salamander Petranka, 1998). Adult and subadult age classes require large cover produces atypically low concentrations of corticosterone in response to objects such as boulders and bedrock crevices, and they feed pre- handling and restraint (Hopkins and DuRant, 2011; DuRant et al., dominantly on crayfish. In most populations, hellbenders are thought to 2015). Baseline concentrations of corticosterone in this species average be primarily nocturnal, but diurnal movement may become more fre- ~0.25 ng/ml and increase to ~1.0 ng/ml after 1–3 h of restraint quent in mid- to late-summer when males become more aggressive and (Hopkins and DuRant, 2011; DuRant et al., 2015). Generally speaking, attempt to commandeer large nest rocks (Noeske and Nickerson 1979; these concentrations are a fraction of those observed in other sala- Humphries and Pauley, 2005) and in the spring following prolonged mander species (Cooperman et al., 2004; Ricciardella et al., 2010; fasting after overwintering (Hopkins, unpublished). Reproduction takes Schubert et al., 2009; Woodley and Lacy, 2010). Understanding whe- place in late August and early September under nest rocks where males ther hellbenders physiologically operate with unusually low con- externally fertilize eggs, and then remain to guard the eggs and larvae centrations of corticosterone, or if they use an alternative glucocorti- until the following April when larvae disperse from the nest (Hopkins, coid, could further our understanding of ecological factors that unpublished). influence the evolutionary divergence of endocrine adaptations among vertebrate lineages. 2.2. Hellbender sampling & treatment Because hellbenders belong to one of the earliest diverging lineages of modern day salamanders (Frost
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